Studies in monkeys and women suggest that unlike traditional estrogen therapy, a diet high in the natural plant estrogens found in soy does not increase the risk of uterine cancer in postmenopausal women, according to Mark Cline, D.V.M., Ph.D., an associate professor of comparative medicine at Wake Forest University Baptist Medical Center.

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Studies in monkeys and women suggest that unlike traditional estrogen therapy, a diet high in the natural plant estrogens found in soy does not increase the risk of uterine cancer in postmenopausal women, according to Mark Cline, D.V.M., Ph.D., an associate professor of comparative medicine at Wake Forest University Baptist Medical Center.

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"These findings give us some confidence that dietary soy doesn't promote uterine cancer and, in fact, may offer a protective effect in some cases," said Cline, who summarized the research studies today in Chicago at the 6th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease.

Cline said there has been much debate about whether high levels of dietary soy are safe for postmenopausal women. Soy products are sometimes sold as a natural alternative to traditional estrogen therapy, which does increase the risk of endometrial cancer. The formulation of hormone therapy designed to address that risk -- a combination of estrogen and progesterone -- has been shown to increase risk of breast cancer.

Soy and some other plants contain estrogen-like compounds called isoflavones or phytoestrogens. These plant estrogens are thousands of times weaker than the estrogen produced by the body, but may be present in much higher concentrations in the blood. Researchers are not certain how plant estrogens and the estrogen produced by the body, or given in pills, act together. One theory is that the plant estrogens bind to cells that have estrogen receptors, such as breast and uterine tissue, and block the effects of the estrogen pills or estrogen made by the body.

Evidence about the safety of soy isoflavones has been mixed. It is known that populations that typically consume diets high in soy have much lower rates of uterine cancer. On the other hand, some laboratory studies in animals have shown that soy isoflavones can stimulate the growth of uterine cells, which is a marker for cancer risk.

Last year, researchers from Italy reported that six women who took soy tablets for up to five years had an increased occurrence of endometrial hyperplasia, a condition in which the lining of the uterus grows too much and may progress to cancer. The study involved 375 women -- half took the soy pills and half took an inactive placebo tablet.

"This observation from this study and its interpretation should be carefully considered," said Cline. "Both human observational studies and several short-term trials of soy isoflavones have not shown any proliferation-inducing effect of soy isoflavones on the uterus."

Cline said that preliminary results from a two-year study of women who consumed 58 milligrams of soy isoflavones a day show no relationship between the soy and endometrial proliferation, and that investigators at other institutions have made similar findings. Similarly, Cline said, monkeys who received soy isoflavones at dietary doses for the equivalent of 10 human years did not show increased risk of endometrial hyperplasia. The monkeys ate one of three diets: soy that didn't contain isoflavones, soy with the isoflavones intact, or soy without isoflavones, but with Premarin, or estrogen therapy, added.

The isoflavone group consumed the human equivalent of about 129 milligrams a day, more than most people would get in a soy-rich diet. The researchers measured numbers of dividing uterine cells and levels of the estrogen produced by the body -- all markers for cancer risk. Monkeys on the soy plus estrogen diet had increased levels of all markers, while monkeys that ate soy with isoflavones did not.

In a short-term study, researchers gave monkeys 10 times the levels of isoflavones normally consumed through diet and again found no effects on the uterus.

Cline said that the results of these studies apply to dietary soy -- and not to the high levels of isoflavones found in soy pills. He also noted that the studies cannot completely rule out the potential for risk. However, he concludes that "the bulk of the experimental evidence points to a protective effect of soy consumption on endometrial cancer risk."

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Other researchers involved in the studies were Charles Wood, D.V.M., and Deirdre Bland, M.D., with Wake Forest Baptist, Adrian Franke, Ph.D., University of Hawaii, and Dolores Froth, M.D., University of Cologne. The research was funded by grants from the National Institutes of Health and the Solae Company.

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